11-1225711-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002458.3(MUC5B):c.101A>G(p.Glu34Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,603,608 control chromosomes in the GnomAD database, including 47,266 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5769 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41497 hom. )

Consequence

MUC5B
NM_002458.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.379

Publications

35 publications found

Variant links:

Genes affected

MUC5B (HGNC:7516): (mucin 5B, oligomeric mucus/gel-forming) This gene encodes a member of the mucin family of proteins, which are highly glycosylated macromolecular components of mucus secretions. This family member is the major gel-forming mucin in mucus. It is a major contributor to the lubricating and viscoelastic properties of whole saliva, normal lung mucus and cervical mucus. This gene has been found to be up-regulated in some human diseases, including sinus mucosa of chronic rhinosinusitis (CRS), CRS with nasal polyposis, chronic obstructive pulmonary disease (COPD) and H. pylori-associated gastric disease, and it may be involved in the pathogenesis of these diseases. [provided by RefSeq, Jul 2010]

MUC5B Gene-Disease associations (from GenCC):

interstitial lung disease
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MUC5B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.632141E-4).

BP6

Variant 11-1225711-A-G is Benign according to our data. Variant chr11-1225711-A-G is described in ClinVar as [Benign]. Clinvar id is 163990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MUC5B	NM_002458.3 link	c.101A>G	p.Glu34Gly	missense_variant	Exon 2 of 49	ENST00000529681.5	NP_002449.2	Q9HC84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MUC5B	ENST00000529681.5 link	c.101A>G	p.Glu34Gly	missense_variant	Exon 2 of 49	5	NM_002458.3	ENSP00000436812.1		Q9HC84
MUC5B	ENST00000525715.5 link	n.159A>G		non_coding_transcript_exon_variant	Exon 2 of 26	1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40760

AN:

151488

Hom.:

5757

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.256

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.298

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.265

GnomAD2 exomes

AF:

0.263

AC:

61220

AN:

233150

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.249

GnomAD4 exome

AF:

0.231

AC:

335568

AN:

1452004

Hom.:

41497

Cov.:

AF XY:

0.232

AC XY:

167441

AN XY:

721394

show subpopulations

African (AFR)

AF:

0.338

AC:

11261

AN:

33332

American (AMR)

AF:

0.235

AC:

10219

AN:

43544

Ashkenazi Jewish (ASJ)

AF:

0.253

AC:

6563

AN:

25912

East Asian (EAS)

AF:

0.484

AC:

19025

AN:

39318

South Asian (SAS)

AF:

0.292

AC:

24688

AN:

84508

European-Finnish (FIN)

AF:

0.355

AC:

18416

AN:

51850

Middle Eastern (MID)

AF:

0.239

AC:

1375

AN:

5746

European-Non Finnish (NFE)

AF:

0.207

AC:

229456

AN:

1107822

Other (OTH)

AF:

0.243

AC:

14565

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

12038

24076

36113

48151

60189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.269

AC:

40809

AN:

151604

Hom.:

5769

Cov.:

AF XY:

0.277

AC XY:

20500

AN XY:

74060

show subpopulations

African (AFR)

AF:

0.331

AC:

13683

AN:

41322

American (AMR)

AF:

0.241

AC:

3677

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

888

AN:

3466

East Asian (EAS)

AF:

0.428

AC:

2170

AN:

5074

South Asian (SAS)

AF:

0.297

AC:

1426

AN:

4796

European-Finnish (FIN)

AF:

0.364

AC:

3823

AN:

10502

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14273

AN:

67880

Other (OTH)

AF:

0.266

AC:

562

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1470

2941

4411

5882

7352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.232

Hom.:

17638

Bravo

AF:

0.263

TwinsUK

AF:

0.202

AC:

748

ALSPAC

AF:

0.213

AC:

819

ESP6500AA

AF:

0.296

AC:

1174

ESP6500EA

AF:

0.205

AC:

1699

ExAC

AF:

0.255

AC:

30679

Asia WGS

AF:

0.377

AC:

1313

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu34Gly in exon 2 of MUC5B: This variant is not expected to have clinical signi ficance because it has been identified in 29.6% (1174/3972) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs2672785). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.20

MetaRNN

Benign

0.00026

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

-0.38

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.15

REVEL

Benign

0.037

Sift

Benign

0.39

Polyphen

0.0

Vest4

0.015

ClinPred

0.00030

GERP RS

0.033

Varity_R

0.019

gMVP

0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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11-1225711-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over